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Somatostatin Receptor Subtype‐4 Agonist Enhances Memory in Apo‐E4 knock‐in Mice
Author(s) -
Witt Ken,
Farr Susan,
Crider A.,
Wooten Joshua,
Sandoval Karin
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb494
Subject(s) - agonist , apolipoprotein e , medicine , endocrinology , receptor , neprilysin , biology , disease , biochemistry , enzyme
This study assessed the impact of somatostatin receptor subtype‐4 (SSTR4) agonist NNC 26‐9100 on learning, memory, cortical neprilysin activity, and blood chemistries in ApoE3 and ApoE4 knock‐in mice. Twelve‐month old ApoE3 and E4 mice were treated with NNC 26‐9100 (10 mg/kg, i.p. daily for 28 days) with all comparisons made to respective vehicle control groups (n=7‐8/group). Statistical significance set at P<0.05. ApoE4 mice, but not ApoE3 mice, spent more time with the novel object (object recognition memory test, day‐28) with NNC 26‐9100 treatment. T‐maze evaluation identified no significant change in learning (day‐21) or memory (day‐28) in either ApoE3 or ApoE4 mice with NNC 26‐9100 treatment. An enhancement in neprilysin activity was found in ApoE3 mice, but not ApoE4 mice, treated with NNC 26‐9100 treatment. Blood chemistries showed enhanced high density lipoprotein (HDL) levels and reduced non‐HDL levels in ApoE4 mice, but not ApoE3 mice, with NNC 26‐9100 treatment. No changes in glucose, insulin, total cholesterol, or triglycerides in either ApoE3 or E4 mice with NNC 26‐9100 treatment.These data show SSTR4 agonist NNC 26‐9100 can mitigate some forms of memory deficit associated with the ApoE4 genotype, but may do so independently of neprilysin activity. Moreover, SSTR4 agonist action enhanced the beneficial HDL levels and reduced the detrimental non‐HDL levels. This work was supported by Southern Illinois University Edwardsville STEP grant.